Hydroxy-halogenated aryl compositions



Patented Sept. 21, 1937 UNITED STATES PATENT? OFFICE-YnYImoxY-nALoGEN'A'rEn Arum coMPo Lucas P. Kyrides,

SITIONS Webster Groves, Mo., assignor,

by ,mesne assignments, to Monsanto Chemical Company, a corporati NoDrawing.

. of manufacturing the same, wherein tertiary halogenated resorcinolsare disclosed-and specifically claimed. I

This invention contemplates a novel class of halogenated phenoliccompositions having inordinate bactericidal, germicidal, as well asgeneral disinfecting properties, and at the same time having asolubility which in many cases is greater than that afiorded bycompounds proposed heretofore. U v

The present invention contemplates phenolic compositions which may berepresented in their essentials by the following formula:

where, in the case of alkyl and acyl derivatives,

R1- is a hydroxyl group and R2 is an alkyl or acyl group having morethan four carbon atoms and not more than twelve carbon. atoms arrangedin a forked chain configuration; or where, in the case of the etherderivatives, R1 is a hydrogen atom and R2 is an alkyloxy group havingmore than four. carbon atoms and not more than twelve carbon atoms, thecarbon atoms being arranged in a forked chain configuration.

The inordinate efficacy of this class of compounds is exemplified by thefact that beta-ethylhexyl-chloro-resorcinol has a phenol coefficient or1000 as measured by the Reddishmethod. The correspondingbromo-resorcinol, tested under the same conditions and on thesame strainof Staphylococcus aureus, evidences a phenol coefiicient of 1300.

In general, compositions contemplated by the present invention having arelatively large number of carbon atoms in the aliphatic chain are moreeffective against Staphylococcus aureus, whereas those having relativelyfewer carbon atoms in the aliphatic chain are more effective againstbacillus-typhosus; Under the circumstances, it-is advantageous to employmixtures of the materials where general disinfection is sought.

Application March 13, SerialNo. 660,524

, (5 Claims; (01. zoo-ism This invention relates to a novel class ofpheon of Delaware forked chainaliphatic acid, having more than four andnotm'ore than twelve carbon atoms, or its'acid chloride with resorcinolin the presence of zinc chloride whereby the corresponding acylresorcinol is formed which subsequently is reduced by the Clemmensenmethod (using hydrochloric acid and amalgamatedzinc) to form the alkylderivative. The alkylation may, of course, be effected by other means ormethods if desired.

The alkyl derivative is finally halogenated by suitablehalogenatingagents such as elemental chlorine, elemental bromine orother suitable halogenating agents. 7 In general, these compositionsmay. be employed in a manner analogous to that employed in connectionwithcorresponding non-halogenated'aliphatic derivatives of phenols inmouthwashes, toothpastes, moth, fungus or mould preventativepreparations as well as in generaldlsinfectants for internal or externaluse.; Various solvents,:such as aqueous glycerol, glycol, ethyl alcohol,etc., may be employed either alone or in admixture with each' other.Obviously, other ingredients may'be added, depending upon the specificintended use to be made of the final product. These may include watersoluble soaps or wetting agents-flavors, coloring matter, as. well asother antiseptic compositions.

The following examples will serve to illustrate a method of preparingproducts embodying the principles of my invention. I ExampleI.Beta-ethyl-hexyl-chloro-resorcinol. This product is prepared by addingslowly and with agitation, 45 parts resorcinol toasolution consisting ofparts of zinc chloride dissolved in 150 parts of alpha-ethyl-hexoic acidhaving the formula:

while maintaining a temperature of -l35 C. After three hours the reactedmixture is diluted with water and the resulting two layers areseparated. The non-aqueous.layer, which contains thev acyl product,ispurified by'dlstillation preferably in vacuo, the yield beingapproximately 91 parts by weight of the ketone. It boils at about 186 C.at 8 mm. pressure and gives a deep red coloration in ferric chloridesolution.

The ketone thus obtained is reduced conveniently by the Clemmensenmethod which consists in subjecting the ketone to the action ofamalgamated zinc anddilute hydrochloric acid. 'The reduction proceedssmoothly at the boiling temperature of the mixture. The product may bepurified bycrystallization from petroleum ether.

The compos'itions'contemplated by thepresent. invention are madeconveniently by reacting a' nol.

Chlorination is effected conveniently by adding a molar equivalent ofsulfuryl chloride to the alkyl resorcinol which previously has beendis-' solved in an inert solvent such as acetic acid or carbontetrachloride. The mono-halogenated product may be crystallized frompetroleum ether containing a small amount of water whereby a hydratedform having a melting point of 56 C. is obtained. The phenol coefllcientof the anhydrous product on Staphylococcus aureus is about 1000.

Example II.Beta-ethyl-hexyl-bromo-resorcinol. This product is made byadding bromine dissolved in acetic acid, slowly, tobeta-ethylhexyl-resorcinol likewise dissolved in acetic acid. Themelting point of the anhydrous product which is obtained byrecrystallization from pee troleum ether and followed by careful dryingin vacuo is 62- C. Its phenol coefllcient is even greater than that ofthe corresponding chloro derivative.

Example IIL- Di-ethyl-ethyl-chloro-resorci- This product may be madeconveniently from di-ethyl-acetic acid or its acid chloride following ingeneral the procedure hereinabove described. The ketone is obtained byadding the acid chloride slowly to resorcinol which is maintained atabout 120 C. Hydrogen chloride is evolved. After the theoretical amountof the acid chloride has been added a small amount of anhydrous zincchloride is introduced and the reaction mixture is maintained at about98- 100 C. forapproximately three hours. The ketone is recovered in theusual manner by washing with water and distilling, preferably in vacuo.

The reduction of the ketone toform the alkyl derivative is eflected inthe usual manner. By subjecting the product to fractional-distillationand crystallization from petroleum ether a product is obtained which.boils at 182 C. at 11 mm. and melts at 73 C. It is chlorinatedconveniently by means of sulfuryl chloride in the presence of a solventsuch as carbon tetrachloride. Crystallization of the chlorinated productfrom petroleum ether containing a small amount of water results 7 in aproduct having a melting point of 59 C. The anhydrous product melts atabout 35 C.

Example IV.-Beta-ethyl-hexyl-iodo-resorcinol may be made by mixing amolar proportion of beta-ethyl-hexyl-resorcinol, which is dissolved in asolvent such as ether, with approximately a molar equivalent of iodine,preferably likewise dissolved in ether. To the mixture there is addedslowly an excess (3 to 5 mol. equivalents) of litharge, the solutionbeing agitated vigorously during the addition and until the color of theiodine disappears.

In general the forked chain alkyl halogenated derivatives appear to bemore soluble in dilute alcoholic solvents than the normal chainhalogenated derivatives and from this standpoint are preferable to thenormal alkyl derivatives for certain p p ses. Thus,di-ethyl-ethyl-chlororesorcinol (melting point anhydrous: 35 C. hydratedform: 59 C.) having the formula on on cl-- ornon is nearly half again assoluble in 10% aqueous alcohol as normal hexyl-chloro-resorcinol.Similarly, beta-ethyl-hexyl-chloro-resorcinol. having the formula:

HO T

CHsCHCHsCHKEHsCHl 5 'ing the formula:

Halogen- CH CH CHCH! l heptyl halogenated resorcinol(ethyl-2-resorcinoll-pentane) having the formula:

on (h s CBsCH I Hal and, nonyl halogenated resorcinol,(propyl-2-resorcinolel-hexane) having the formula:

Halogen- "CHICH CaHn These products possess a common high germicidalpower and low toxicity and are suitable for the purposes herein setforth. It will be apparent from the foregoing description that thepresent invention afiords a novel class of compositions which possessstrong germicidal properties and may thereafter be employed in verysmall amounts without defeating the purpose for which they are intended.While representative examples of the application of the principles ofthe invention have been set forth, these are illustrative only, sincethe invention is susceptible to many variations without departing fromthe scope thereof. Thus, corresponding poly halogenated nuclearsubstituted products are contemplated as well as products wherein thereare Joined to the benzene nucleus additional organic substituent groups,to wit: and alkyl group, an aralkyl group which group may contain anuclear substituted halogen, an example of which is para-chloro-benzylCsH4C1CH2-, a cyclohenl group, a hydroxyl or an alkyl ether group.

What I claim is:

1. A halogenated dihydroxy benzene composition embodying the aliphaticgroup-CHzR. said group being joined to a carbon atom of the benzenering, R being a secondary alkyl radical containing more than three andnot more than eleven carbon atoms.

2. A halogenated resorcinol composition embodying the aliphaticgroup-CHzR, said group being joined to a carbon atom of the benzenering, R. being a secondary alkyl radical containing more than three andnot more than eleven carbon atoms.

3. A halogenated beta-ethyl-hexyl-resorcinol. 4.Beta-etbyl-hexyl-chloro-resorcinol. 5.Beta-ethyl-hexyl-bromo-resorcinol. 6. A halogenated phenolic compositioncharac- .7

tcrized by its inordinate germicidal properties where R; is a hydroxylgroup and R: is the alkyl which may be represented structurally:group-Cm joined to the carbon atom of the ring, B being a secondaryalkyi radical containing more than three and not more than eleven car- 5bon atoms. 5

LUCAS P. KYRIDES.

